HBeAg水平与免疫清除期慢性乙型肝炎患者的临床病理关系

目的 探讨免疫清除(IC)期慢性乙型肝炎(CHB)患者血清HBeAg水平与肝脏炎症活动度分级(G)、纤维化分期(S)的关系.方法 连续收集2007年3月至2010年6月福建医科大学附属第一医院肝病中心确诊为IC期的CHB患者,同步行肝组织病理学检查及血清HBeAg和HBVDNA检测.Spearman等级相关分析法判断HBeAg水平与肝脏病理学分级间的相关性,受试者工作曲线(ROC)法判断HBeAg水平对肝脏G分级及S分期的预测价值.结果 共249例IC期CHB患者纳入本研究,G1～G4患者血清HBeAg水平分别为(2.93±2.85)、(2.96±2.74)、(2.69±2.67)和(2.30±2.41) lg s/co,S1～S4患者血清HBeAg水平分别为(2.99±2.74)、(2.89±2.73)、(2.58±2.55)和(2.32±2.44)lg s/co,提示4组患者G分级及S分期间HBeAg水平差异均有统计学意义(x2值分别为47.13和74.12,均P＜0.01).Spearman等级相关分析提示血清HBeAg水平与G分级、S分期呈负相关(r值分别为-0.418和-0.532,均P＜0.01).判断G≥3和G≥4,S≥3和S≥4患者的受试者工作曲线下面积(AUC)分别为0.74和0.73,0.80和0.77; HBeAg最佳截点分别为2.95、2.64、2.99和2.82 lg s/co.结论 在IC期CHB中,肝组织学G分级及S分期与HBeAg水平呈负相关.结合HBeAg水平,有助于肝脏病理学变化程度的判断.     

HBsAg定量与HBeAg阴性慢性乙型肝炎患者肝脏组织学相关性分析

目的 探讨HBsAg定量水平对HBeAg阴性慢性乙型肝炎(CHB)患者肝脏组织学评分的预测价值.方法 入组100例,5.00×102拷贝/ml≤HBV DNA＜104拷贝/ml,ALT正常的HBeAg阴性CHB患者,其中男48例,女52例,年龄均＞40岁.根据HBsAg定量水平被随机分成了2组,A组(HBsAg定量＜1500 IU/ml)61例和B组(HBsAg定量≥1500 IU/ml)39例.2组患者均检测血清HBV DNA水平,HBsAg定量,肝组织学G、S分期,并进行相关性分析.结果 在HBsAg定量低水平时,肝脏炎症活动度(G≥2)百分比或者肝脏纤维化(S≥2)百分比分别为14.75％与6.56％,在HBsAg定量较高水平时,肝脏炎症活动度(G≥2)百分比和肝脏纤维化(S≥2)百分比分别为89.74％与79.49％,肝脏炎症程度及纤维化程度评分与HBsAg定量无明显相关性.结论 对HBeAg阴性CHB患者来说,HBsAg定量水平与肝脏炎症活动度及肝纤维化程度无明显相关性,故肝脏组织学检查仍是必不可少.     

血清铜蓝蛋白水平与慢性乙型肝炎患者临床病理关系的初步研究

目的 探讨慢性乙型肝炎(CHB)患者血清铜蓝蛋白(CP)水平与肝脏炎症活动度分级、纤维化分期的关系,建立肝纤维化分级无创模型并分析其诊断价值.方法 2009年1月至2011年6月于福建医科大学附属第一医院肝病中心确认的CHB患者148例,同步进行肝组织病理学、血清CP及生物化学指标检查.Spearman等级相关分析法判断CP水平与肝脏病理学分级之间的相关性;Logistic回归分析法分析相关指标的诊断意义.构建肝脏纤维化诊断预测模型,受试者工作曲线(ROC)法评价模型的诊断价值.结果 148例CHB患者炎症活动度分级G1、G2、G3、G4的血清CP平均值分别为(212.5±34.9)、(205.5±32.0)、(201.4±37.7)和(172.8±20.4) mg/L,ANOVA分析提示4组炎症活动度分级间CP水平的差异有统计学意义(F=6.309,P＜0.01);纤维化分期S1、S2、S3、S4的血清CP平均水平分别为(217.4±32.3)、(206.0±37.7)、(194.2±29.8)和(179.7±30.4)mg/L,ANOVA分析提示纤维化分期间CP的差异有统计学意义(F=8.608,P＜0.01).Spearman等级相关分析法分析提示,CP与炎症活动度分级(r=-0.316,P＜0.01)以及纤维化分期(r=-0.404,P＜0.01)均呈负相关关系.应用ROC分别建立CP水平对S≥2、S≥3、S=4的诊断曲线,曲线下面积(AUC)分别为0.71、0.70和0.72.经Logistic回归分析,筛选出模型-1(S≥2)、模型-2(S≥3)、模型-3(S=4)组包括CP、甲胎蛋白、胆碱酯酶、PLT、年龄的肝纤维化独立预测因子,最终构建数学模型并计算肝纤维化评分,模型-1、模型-2、模型-3的AUC分别为0.84、0.83和0.87,准确率分别为71.8％、80.3％和79.2％.结论 CHB患者的血清CP水平与肝脏炎症活动度分级、纤维化分期呈负相关关系,随病理分级的增加而呈阶梯状降低.CP水平可作为无创性判断肝脏纤维化状态的一项重要指标,纳入CP而构建的肝纤维化预测模型对CHB肝纤维化肝硬化有较好的诊断价值.     

慢性乙型肝炎不同肝纤维化分期的肝实质细胞体积所分摊的HBsAg表达变化

目的 观察慢性乙型肝炎免疫清除期肝纤维化S1、S2、S3和S4期,相同肝实质细胞体积所分摊HBsAg表达的动态变化. 方法 对89例HBeAg阳性慢性乙型肝炎免疫清除期患者应用电化学发光法检测肝纤维化S1、S2、S3和S4期血清HBsAg的水平;进一步用相同肝实质细胞体积分摊并且两两比较肝纤维化S1、S2、S3和S4期血清HBsAg的水平.使用SPSS 15.0统计软件,组间用两两比较,采用ANOVA检验进行分析. 结果 肝纤维化S1、S2、S3和S4期的血清HBsAg水平分别为(227.2±237.7)IU/ml、(211.0±131.4)IU/ml、(300.2±144.6) IU/ml和(278.7±148.8) IU/ml,四组之间两两比较,差异无统计学意义.用相同肝实质细胞体积进行分摊,在肝纤维化S1、S2、S3和S4期的HBsAg水平分别为(343.9±359.8)IU/ml、(336.4±209.5)IU/ml、(508.7±245.1)IU/ml和(525.2±274.8) IU/ml,四组两两比较,F=3.045,P=0.033,差异有统计学意义,其中,S1与S3、S1 与S4、S2与S3和S2与S4比较,P值分别为0.041、0.046、0.028和0.034,差异均有统计学意义.结论 在慢性乙型肝炎免疫清除期中,随着肝纤维化从S1期向S4期进展,相同肝实质细胞体积所分摊的HBsAg表达逐渐增强.     

HBeAg阳性和阴性慢性乙型肝炎患者肝组织学与血清学关系的比较

目的 研究慢性乙型肝炎(CHB)患者(1×ULN≤ALT≤2×ULN)肝组织学与血清学的关系.方法 对全国多中心516例CHB患者(1×ULN≤ALT≤2×ULN)行血清学及肝穿刺病理检查,依据血清HBeAg表达水平将患者分为HBeAg阳性组和HBeAg阴性组,分析两组肝组织病理学与血清学指标的相关性.结果 HBeAg阳性患者肝组织炎症分级和肝纤维化分期与血清HBsAg和HBeAg表达水平呈负相关(P＜0.01),与血清透明质酸(HA)和α2-巨球蛋白水平呈正相关(P＜0.01),与血清HBVDNA水平无明显相关性;HBeAg阴性患者肝组织炎症分级和肝纤维化分期与血清HBV DNA水平呈正相关(P＜0.01),与HBsAg、HA和α2-巨球蛋白等无明显相关性.结论 血清HBV DNA可做为HBeAg阴性CHB患者肝脏病变程度的有效预测指标,HBsAg、HBeAg、HA和α2-巨球蛋白均可做为HBeAg阳性CHB患者肝组织损伤的预测指标.     

35例HBeAg阴性慢性乙型肝炎患者肝组织病理学分析

目的探讨HBeAg阴性CHB患者肝组织病理学分级分期与血清ALT和HBV DNA水平的关系。方法在35例HBeAg阴性CHB患者,行肝穿刺活检术和常规检测血清HBV DNA和ALT。结果在35例HBeAg阴性CHB患者中,肝组织学检查示G1S0者1例,G1S1者6例,G1S2者7例,G1S3者1例,G2S1者1例,G2S2者8例,G2S3者3例,G3S2者4例,G3S3者4例;G1患者血清HBV DNA水平(3.2±2.3lgcopies/ml)较G2/G3者低(分别为5.4±1.5lgcopies/ml和5.0±1.4lgcopies/ml,P<0.05);S0-2患者血清ALT水平为161.0±251.5U/L,显著高于S3者(45.6±23.4U/L,P<0.05);肝组织炎症分级与纤维化分期呈显著正相关(r=0.543,P<0.01);血清HBV DNA水平与肝组织炎症分级呈明显正相关(r=0.462,P<0.01),而与纤维化分期无明显相关(r=0.083,P>0.05);血清ALT水平与肝组织炎症分级或纤维化分期均无相关性(r值分别为0.18和-0.213,P>0.05)。结论 HBeAg阴性CHB患者血清HBV DNA水平与肝组织炎症分级高度正相关,但两者的关系仍需进一步深入探讨。     

慢性乙型肝炎患者HBVDNA载量与肝组织炎症及纤维化程度的相关性分析

目的研究慢性乙型肝炎(CHB)患者血清HBV DNA载量与肝组织炎症及纤维化程度间的相关性。方法将169例CHB患者根据血清HBeAg分为HBeAg阳性组(110例)和HBeAg阴性组(59例),回顾性分析血清HBV DNA载量与肝组织病理炎症分级、纤维化分期之间关系。结果 HBeAg阳性组与HBeAg阴性组血清HBV DNA载量分别为(6.9±1.3)log10拷贝/ml和(4.7±1.8)log10拷贝/ml,两组比较差异有统计学意义(P=0.024)。HBeAg阳性组患者肝组织炎症活动度G1组为9例、G2组为80例、G3~4组为21例,其血清HBV DNA载量分别为(5.7±1.4)log10拷贝/ml、(6.4±1.8)log10拷贝/ml、(7.2±1.1)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异无统计学意义(P=0.069)。肝组织纤维化程度S1组为28例、S2组为50例、S3~4组为32例,其血清HBV DNA载量分别为(6.9±1.1)log10拷贝/ml、(6.9±1.4)log10拷贝/ml、(6.8±4.2)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异无统计学意义(P=0.079)。HBeAg阴性组患者肝组织炎症活动度G1组为6例、G2组为19例、G3~4组为34例,其血清HBV DNA载量分别为(2.2±1.9)log10拷贝/ml、(4.9±1.5)log10拷贝/ml、(5.4±1.8)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异有统计学意义(P=0.014);肝组织纤维化程度S1组为12例、S2组为30例、S3~4组为17例,其血清HBV DNA载量分别为(2.6±4.1)log10拷贝/ml、(5.3±1.3)log10拷贝/ml、(5.6±1.7)log10拷贝/ml,3组血清HBV DNA载量比较,差异有统计学意义(P=0.026)。结论 HBeAg阳性CHB患者血清HBV DNA载量与肝组织炎症及纤维化程度无显著相关。HBeAg阴性CHB患者血清HBV DNA载量较高者,其肝组织炎症及纤维化程度较高。     

前白蛋白检测在慢性乙型肝炎病理分级中的价值

目的：明确血清前白蛋白对判断慢性乙型肝炎患者肝脏炎症分级及纤维化分期的价值。方法：检测78例经肝活检证实的慢性乙型肝炎患者血清PAB水平的变化，并将其与肝活检组织的炎症分级和纤维化分期进行对照研究。结果：肝脏病理组织炎症分为G1-G4级，纤维化分为Su-S4期。炎症轻重两组间PAB差异有显著性意义（P〈0．01）。随着纤维化程度的增加，PAB逐渐下降，且S4及S0、S1、S2和S3比较差异有显著性意义（P〈0．01）。PAB与炎症分级及纤维化分期之间相关性均非常显著（P〈0．01）。结论：PAB能较好地反映慢性乙型肝炎患者肝脏的炎症活动水平，并能较敏感地反映慢性乙型肝炎患者肝脏的纤维化程度，在一定程度上可以提示早期肝硬化。     

HBeAg阴性慢性乙型肝炎患者血清HBsAg水平在不同肝组织炎症分级和纤维化分期的变化

目的 探讨HBeAg阴性慢性乙型肝炎患者血清HBsAg水平以及经相同肝实质细胞体积(肝细胞数量)分摊后的血清HBsAg水平在不同肝组织炎症分级和纤维化分期的动态变化情况. 方法 对144例HBeAg阴性慢性乙型肝炎患者,应用电化学发光法检测血清HBsAg水平.分别两两比较肝组织炎症1、2、3和4级以及Ⅰ、Ⅱ、Ⅲ和Ⅳ期纤维化时血清HBsAg的水平以及经相同肝实质细胞体积分摊后的血清HBsAg水平.组间均数比较采用单因素方差分析,进一步两两比较采用LSD-t检验.结果 肝组织炎症1、2、3、4级时血清HBsAg水平(COI/ml)分别为6 036.4±2 729.4、6 704.6±2 457.5、6 332.2±2 409.0和6226.2±2 716.0,各组之间差异无统计学意义(F分摊前=0.564,P=0.640);但经相同肝实质细胞体积(肝细胞数量)分摊后,肝组织炎症1、2、3、4级时的血清HBsAg水平(COI/ml)分别为9 174.8±4 142.0、10743.1±3950.3、11 078.0±4 230.0和11 540.5±5 058.8,各组之间差异有统计学意义(F分摊后=27.354,P＜ 0.01).肝纤维化Ⅰ、Ⅱ、Ⅲ和Ⅳ期时血清HBsAg水平(COI/ml)分别为6 222.1±2 665.4、6 706.8±2 623.8、6 004.5±2 625.5和6 455.6±2 344.4,各组之间差异无统计学意义(F分摊前=0.768,P=0.513);但经相同肝实质细胞体积(肝细胞数量)分摊后,肝纤维化Ⅰ、Ⅱ、Ⅲ和Ⅳ期时血清HBsAg水平(COI/ml)分别为9 417.5±4 034.2、10 093.3±4 183.4、10 177.1±4 445.0和12 166.6±4 418.5,各组之间差异有统计学意义(F分摊后=57.077,P＜ 0.01).结论 HBeAg阴性慢性乙型肝炎患者,相同肝实质细胞体积(肝细胞数量)分摊后的血清HBsAg水平,而非血清HBsAg水平,随肝组织病理进展而不断增加.     

免疫清除期相同肝实质细胞体积分摊的血清HBV DNA载量与肝组织炎症分级的关系

目的 阐明慢性乙型肝炎自然病程中免疫清除期相同肝实质细胞体积分摊的血清HBVDNA载量水平与肝组织炎症分级的关系. 方法 使用荧光多聚酶链反应分别检测和比较慢性乙型肝炎免疫清除期患者肝组织病理炎症分级1、2、3、4级的血清HBV DNA载量,以及肝组织炎症分级1、2,3、4级所在肝纤维化分期用相同肝实质细胞体积分摊的血清HBV DNA载量.多组资料两两比较采用ANOVA检验分析. 结果 176例处于免疫清除期慢性乙型肝炎患者肝组织病理学炎症分级1、2、3、4级血清HBV DNA载量分别为(8.20×10~5±9.11×10~1)拷贝/ml、(16×10~6±5.96×10~1)拷贝/ml、(8.12×10~5±8.01×10~1)拷贝/ml和(2.08×10~6±3.69×10~1)拷贝/ml,差异无统计学意义(P>0.05).然而,肝组织病理炎症1、2、3、4级所在肝纤维化分期用相同肝脏实质细胞体积分摊后的血清HBV DNA载量分别为(9.24×10~8±9.35×10~2)拷贝/ml、(5.33×10~9±7.56×10~2)拷贝/ml、(1.06×10~(10)±1.77×10~3)拷贝/ml、(3.31×10~(11)± 5.18×10~2)拷贝/ml,差异有统计学意义(P<0.05).结论 在HBV感染的自然病程中,从免疫耐受期进入免疫清除期后,肝细胞反复出现炎症,坏死,同时伴纤维组织增生.不同肝纤维化分期中相同肝实质细胞体积分摊的血清HBV DNA载量水平与肝组织炎症分级有关.     

慢性乙型肝炎患者肝细胞内乙型肝炎核心抗原阳性的临床意义

目的探讨CHB患者肝组织HBcAg阳性的意义。方法对200例CHB患者应用荧光聚合酶链反应（FQ-PCR）法精确定量检测血清HBV DNA含量。患者均检测血清中HBeAg含量,同时进行肝活组织检查,应用免疫组织化学技术检测HBcAg情况,并进行相关性分析。结果按测定血清HBV DNA水平,分为A组（＜3 log10拷贝/ml）20例,B组（≥3 log10拷贝/ml-＜5 log10拷贝/ml）13例,C组（≥5 log10拷贝/ml～＜6 log10拷贝/ml）24例,D组（≥6 log10拷贝/ml～＜8 log10拷贝/ml）116例,E组（≥8 log10拷贝/ml）27例。肝组织HBcAg阳性者175例,占87．5％,A组HBcAg阳性率55．0％（11/20）,B组53．8％（7/13）,C组75．0％（18/24）,D组96．6％（112/116）,E组100．0％（27/27）,HBcAg阳性率与血清HBV DNA水平之间呈显著正相关（r=0．80,P＜0．01）。血清HBV DNA水平高低与HBeAg阳性率之间呈显著正相关（r=0．47,P＜0．01）。其中20例HBV DNA阴性者中（A组）,HBeAg阳性者5例（25％）,HBcAg阳性者11例（55％）；15例HBV DNA阴性且HBeAg阴性者中有7例HBcAg阳性,占46．7％。结论CHB患者肝组织HBcAg阳性能更可靠地反映肝细胞内HBV复制状态。检测肝组织内HBcAg对CHB患者疗效评价和对治疗反应性的预测更具有临床意义。     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.